Skeletal muscle proteostasis in health and disease states: the role of stable isotopes in contemporary clinical nutrition research

AbstractEndospore-formers in the human microbiota are well adapted for host-to-host transmission, and an emerging consensus points to their role in determining health and disease states in the gut. The human gut, more than any other environment, encourages the maintenance of endospore formation, with recent culture-based work suggesting that over 50% of genera in the microbiome carry genes attributed to this trait. However, there has been limited work on the ecological role of endospores and other stress-resistant cellular states in the human gut. In fact, there is no data to indicate whether organisms with the genetic potential to form endospores actually form endosporesin situand how sporulation varies across individuals and over time. Here, we applied a culture-independent protocol to enrich for endospores and other stress-resistant cells in human feces to identify variation in these states across people and within an individual over time. We see that cells with resistant states are more likely than those without to be shared among multiple individuals, which suggests that these resistant states are particularly adapted for cross-host dissemination. Furthermore, we use untargeted fecal metabolomics in 24 individuals and within a person over time to show that these organisms respond to shared environmental signals, and in particular, dietary fatty acids, that likely mediate colonization of recently disturbed human guts.

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The human cortical autonomic network and volitional exercise in health and disease

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2018-0305 ◽

2018 ◽

Vol 43 (11) ◽

pp. 1122-1130 ◽

Cited By ~ 7

Author(s):

Baraa K. Al-Khazraji ◽

J. Kevin Shoemaker

Keyword(s):

Current Knowledge ◽

Insular Cortex ◽

Cardiovascular Control ◽

Anterior Cingulate ◽

Disease States ◽

Autonomic Activation ◽

Imaging Research ◽

Health And Disease ◽

Cortical Regions

The autonomic nervous system elicits continuous beat-by-beat homeostatic adjustments to cardiovascular control. These modifications are mediated by sensory inputs (e.g., baroreceptors, metaboreceptors, pulmonary, thermoreceptors, and chemoreceptors afferents), integration at the brainstem control centres (i.e., medulla), and efferent autonomic neural outputs (e.g., spinal, preganglionic, and postganglionic pathways). However, extensive electrical stimulation and functional imaging research show that the brain’s higher cortical regions (e.g., insular cortex, medial prefrontal cortex, anterior cingulate cortex) partake in homeostatic regulation of the cardiovascular system at rest and during exercise. We now appreciate that these cortical areas form a network, namely the “cortical autonomic network” (CAN), which operate as part of a larger central autonomic network comprising 2-way communication of cortical and subcortical areas to exert autonomic influence. Interestingly, differential patterns of CAN activity and ensuing cardiovascular control are present in disease states, thereby highlighting the importance of considering the role of CAN as an integral aspect of cardiovascular regulation in health and disease. This review discusses current knowledge on human cortical autonomic activation during volitional exercise, and the role of exercise training on this activation in both health and disease.

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The role of vitamins and minerals in modulating the expression of microRNA

Nutrition Research Reviews ◽

10.1017/s0954422414000043 ◽

2014 ◽

Vol 27 (1) ◽

pp. 94-106 ◽

Cited By ~ 23

Author(s):

Emma L. Beckett ◽

Zoe Yates ◽

Martin Veysey ◽

Konsta Duesing ◽

Mark Lucock

Keyword(s):

Gene Expression ◽

Food Sources ◽

Transcriptional Level ◽

Disease States ◽

Regulatory Circuit ◽

Non Coding Rna ◽

Epigenetic Machinery ◽

Health And Disease ◽

Expression Potential

A growing number of studies in recent years have highlighted the importance of molecular nutrition as a potential determinant of health and disease. In particular, the ability of micronutrients to regulate the final expression of gene products via modulation of transcription and translation is now being recognised. Modulation of microRNA (miRNA) by nutrients is one pathway by which nutrition may mediate gene expression. miRNA, a class of non-coding RNA, can directly regulate gene expression post-transcriptionally. In addition, miRNA are able to indirectly influence gene expression potential at the transcriptional level via modulation of the function of components of the epigenetic machinery (DNA methylation and histone modifications). These mechanisms interact to form a complex, bi-directional regulatory circuit modulating gene expression. Disease-specific miRNA profiles have been identified in multiple disease states, including those with known dietary risk factors. Therefore, the role that nutritional components, in particular, vitamins and minerals, play in the modulation of miRNA profiles, and consequently health and disease, is increasingly being investigated, and as such is a timely subject for review. The recently posited potential for viable exogenous miRNA to enter human blood circulation from food sources adds another interesting dimension to the potential for dietary miRNA to contribute to gene modulation.

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Skeletal Muscle Na,K-ATPase as a Target for Circulating Ouabain

International Journal of Molecular Sciences ◽

10.3390/ijms21082875 ◽

2020 ◽

Vol 21 (8) ◽

pp. 2875 ◽

Cited By ~ 3

Author(s):

Violetta V. Kravtsova ◽

Elena V. Bouzinova ◽

Vladimir V. Matchkov ◽

Igor I. Krivoi

Keyword(s):

Skeletal Muscle ◽

Diaphragm Muscle ◽

Hindlimb Suspension ◽

Resting Potential ◽

Human Red Blood Cells ◽

Central Nervous Systems ◽

Health And Disease ◽

Specific Increase ◽

20 Nm

While the role of circulating ouabain-like compounds in the cardiovascular and central nervous systems, kidney and other tissues in health and disease is well documented, little is known about its effects in skeletal muscle. In this study, rats were intraperitoneally injected with ouabain (0.1–10 µg/kg for 4 days) alone or with subsequent injections of lipopolysaccharide (1 mg/kg). Some rats were also subjected to disuse for 6 h by hindlimb suspension. In the diaphragm muscle, chronic ouabain (1 µg/kg) hyperpolarized resting potential of extrajunctional membrane due to specific increase in electrogenic transport activity of the α2 Na,K-ATPase isozyme and without changes in α1 and α2 Na,K-ATPase protein content. Ouabain (10–20 nM), acutely applied to isolated intact diaphragm muscle from not injected rats, hyperpolarized the membrane to a similar extent. Chronic ouabain administration prevented lipopolysaccharide-induced (diaphragm muscle) or disuse-induced (soleus muscle) depolarization of the extrajunctional membrane. No stimulation of the α1 Na,K-ATPase activity in human red blood cells, purified lamb kidney and Torpedo membrane preparations by low ouabain concentrations was observed. Our results suggest that skeletal muscle electrogenesis is subjected to regulation by circulating ouabain via the α2 Na,K-ATPase isozyme that could be important for adaptation of this tissue to functional impairment.

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The role of tissue factor and tissue factor pathway inhibitor in health and disease states

Journal of Veterinary Emergency and Critical Care ◽

10.1111/j.1476-4431.2008.00380.x ◽

2009 ◽

Vol 19 (1) ◽

pp. 23-29 ◽

Cited By ~ 18

Author(s):

Louis A. DelGiudice ◽

George A. White

Keyword(s):

Tissue Factor ◽

Tissue Factor Pathway Inhibitor ◽

Disease States ◽

Health And Disease ◽

Tissue Factor Pathway

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Muscling in on mitochondrial sexual dimorphism; role of mitochondrial dimorphism in skeletal muscle health and disease

Clinical Science ◽

10.1042/cs20160940 ◽

2017 ◽

Vol 131 (15) ◽

pp. 1919-1922 ◽

Cited By ~ 3

Author(s):

Gareth A. Nye ◽

Giorgos K. Sakellariou ◽

Hans Degens ◽

Adam P. Lightfoot

Keyword(s):

Skeletal Muscle ◽

Sexual Dimorphism ◽

Mitochondrial Function ◽

Gambogic acid identifies an isoform-specific druggable pocket in the middle domain of Hsp90β

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1606655113 ◽

2016 ◽

Vol 113 (33) ◽

pp. E4801-E4809 ◽

Cited By ~ 28

Author(s):

Kendrick H. Yim ◽

Thomas L. Prince ◽

Shiwei Qu ◽

Fang Bai ◽

Patricia A. Jennings ◽

...

Keyword(s):

Molecular Chaperone ◽

Drug Targets ◽

Heat Shock Protein 90 ◽

Hsp90 Inhibitor ◽

Gambogic Acid ◽

Disease States ◽

Middle Domain ◽

Health And Disease ◽

A Site

Because of their importance in maintaining protein homeostasis, molecular chaperones, including heat-shock protein 90 (Hsp90), represent attractive drug targets. Although a number of Hsp90 inhibitors are in preclinical/clinical development, none strongly differentiate between constitutively expressed Hsp90β and stress-induced Hsp90α, the two cytosolic paralogs of this molecular chaperone. Thus, the importance of inhibiting one or the other paralog in different disease states remains unknown. We show that the natural product, gambogic acid (GBA), binds selectively to a site in the middle domain of Hsp90β, identifying GBA as an Hsp90β-specific Hsp90 inhibitor. Furthermore, using computational and medicinal chemistry, we identified a GBA analog, referred to as DAP-19, which binds potently and selectively to Hsp90β. Because of its unprecedented selectivity for Hsp90β among all Hsp90 paralogs, GBA thus provides a new chemical tool to study the unique biological role of this abundantly expressed molecular chaperone in health and disease.

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Measurement of nitrate and nitrite in biopsy-sized muscle samples using HPLC

Journal of Applied Physiology ◽

10.1152/japplphysiol.00625.2018 ◽

2018 ◽

Vol 125 (5) ◽

pp. 1475-1481 ◽

Cited By ~ 2

Author(s):

Ashley D. Troutman ◽

Edgar J. Gallardo ◽

Mary Beth Brown ◽

Andrew R. Coggan

Keyword(s):

Skeletal Muscle ◽

Whole Body ◽

Oxidoreductase Activity ◽

Bead Beating ◽

Health And Disease ◽

Text Content ◽

Nitrate And Nitrite ◽

Triton X ◽

Mechanical Homogenization

Studies of rats have indicated that skeletal muscle plays a central role in whole-body nitrate ([Formula: see text])/nitrite ([Formula: see text])/nitric oxide (NO) metabolism. Extending these results to humans, however, is challenging due to the small size of needle biopsy samples. We therefore developed a method to precisely and accurately quantify [Formula: see text] and [Formula: see text] in biopsy-sized muscle samples. [Formula: see text] and [Formula: see text] were extracted from rat soleus samples using methanol combined with mechanical homogenization + ultrasound, bead beating, pulverization at liquid N2temperature or pulverization + 0.5% Triton X-100. After centrifugation to remove proteins, [Formula: see text] and [Formula: see text] were measured using HPLC. Mechanical homogenization + ultrasound resulted in the lowest [Formula: see text] content (62 ± 20 pmol/mg), with high variability [coefficient of variation (CV) >50%] across samples from the same muscle. The [Formula: see text]/[Formula: see text] ratio (0.019 ± 0.006) was also elevated, suggestive of [Formula: see text] reduction during tissue processing. Bead beating or pulverization yielded lower [Formula: see text] and slightly higher [Formula: see text] levels, but reproducibility was still poor. Pulverization + 0.5% Triton X-100 provided the highest [Formula: see text] content (124 ± 12 pmol/mg) and lowest [Formula: see text]/[Formula: see text] ratio (0.008 ± 0.001), with the least variability between duplicate samples (CV ~15%). These values are consistent with literature data from larger rat muscle samples analyzed using chemiluminescence. Samples were stable for at least 5 wk at −80°C, provided residual xanthine oxidoreductase activity was blocked using 0.1 mmol/l oxypurinol. We have developed a method capable of measuring [Formula: see text] and [Formula: see text] in <1 mg of muscle. This method should prove highly useful in investigating the role of skeletal muscle in [Formula: see text]/[Formula: see text]/NO metabolism in human health and disease.NEW & NOTEWORTHY Measurement of nitrate and especially nitrite in small, i.e., biopsy-sized, muscle samples is analytically challenging. We have developed a precise, accurate, and convenient method for doing so using an affordable commercial HPLC system.

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Novel antibodies for the simple and efficient enrichment of native O-GlcNAc modified peptides

10.1101/2021.05.28.446228 ◽

2021 ◽

Author(s):

Rajan A Burt ◽

Borislav Dejanovic ◽

Hayley J Peckham ◽

Kimberly A Lee ◽

Xiang Li ◽

...

Keyword(s):

High Specificity ◽

Tissue Samples ◽

Post Translational Modifications ◽

Disease States ◽

Modified Peptides ◽

Health And Disease ◽

Time Required ◽

Glcnac Transferase ◽

Enrichment Strategy

Antibodies against post-translational modifications (PTMs) such as lysine acetylation, ubiquitin remnants, or phosphotyrosine have resulted in significant advances in our understanding of the fundamental roles of PTMs in biology. However, the roles of a number of PTMs remain largely unexplored due to the lack of robust enrichment reagents. The addition of N-acetylglucosamine to serine and threonine residues (O-GlcNAc) by the O-GlcNAc transferase (OGT) is a PTM implicated in numerous biological processes and disease states but with limited techniques for its study. Here, we evaluate a new mixture of anti-O-GlcNAc monoclonal antibodies for the immunoprecipitation of native O-GlcNAcylated peptides from cells and tissues. The anti-O-GlcNAc antibodies display good sensitivity and high specificity toward O-GlcNAc-modified peptides, and do not recognize O-GalNAc or GlcNAc in extended glycans. Applying this antibody-based enrichment strategy to synaptosomes from mouse brain tissue samples, we identified over 1,300 unique O-GlcNAc-modified peptides and over 1,000 sites using just a fraction of sample preparation and instrument time required in other landmark investigations of O-GlcNAcylation. Our rapid and robust method greatly simplifies the analysis of O-GlcNAc signaling and will help to elucidate the role of this challenging PTM in health and disease.

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